1. Field of the Invention
The present invention relates to a patch and a method for producing the patch. More specifically, the present invention relates to a patch using oxybutynin hydrochloride as a drug and a method for producing the patch.
2. Related Background Art
Conventionally, the oral administration method using a tablet, a capsule, a syrup, or the like has been known as a drug administration method. In recent years, the transdermal administration method has been studied in which a drug is transdermally administered by using a patch. The method using a patch can solve problems associated with the oral administration method, and has advantages such as reduction in frequency of administration, improvement in compliance, and ease of administration and discontinuation. For these reasons, the transdermal administration method is expected as a drug administration method useful especially in a case of elderly or child patients.
The stratum corneum of the normal skin has a barrier function of preventing foreign substances from entering the body. Because of the barrier function, the use of conventional patches often ends up with insufficient transdermal absorption of the formulated drug ingredient. Moreover, since the stratum corneum is highly lipophilic, the skin penetrability of a drug is extremely low, in general.
In a generally known method for enhancing the skin penetrability of a drug in the transdermal administration method, the drug is contained at a supersaturated concentration in a transdermal preparation, and the difference in concentration gradient of the drug is utilized, as described in “Pharmaceutical Skin Penetration Enhancement,” edited by K A Walters and J Hadgraft, (the United States), Vol. 59, Marcel Dekker, 1993, pp. 243-267. For example, Japanese Patent Application Publication No. Sho 63-93714 (Patent Literature 1) describes a patch comprising an adhesive agent layer containing a drug at a supersaturated concentration. However, the method in which a drug is contained at a supersaturated concentration in an adhesive agent layer of a patch involves an increased possibility of crystal precipitation of the drug. Hence, the method has problems associated with the crystal precipitation, such as reduction in cohesiveness and adhesion of the adhesive agent layer and reduction in skin penetrability due to a reduced drug release rate. Furthermore, Patent Literature 1 describes melting of crystals of the drug precipitated during storage by heating before use. However, such a method requires the heating operation every time the patch is used, and hence has problems in terms of convenience and ease of administration.
Meanwhile, International Application Japanese-Phase Publication No. 2010-521525 (Patent Literature 2) proposes a transdermal delivery device in which a drug is contained at a supersaturated concentration in an amorphous form in an adhesive matrix. Oxybutynin is listed as an example of the drug. Moreover, as methods for obtaining the drug at a supersaturated concentration in an amorphous form, Patent Literature 2 describes a method in which an adhesive matrix solution containing the drug at a subsaturated concentration is used, or a method in which an adhesive matrix containing the drug at a supersaturated concentration is heated at a temperature exceeding the melting point of the drug. However, when the drug is caused to be present in an amorphous form in the adhesive agent layer in such a manner, the drug is still in a solid form. Hence, the method has the following problems: insufficient pharmaceutical physical properties such as adhesion and cohesiveness; crystal precipitation with the elapse of time; and low release rate of the drug at an initial stage of application of the patch.
On the other hand, Japanese Patent Application Publication No. 2004-83519 (Patent Literature 3) describes a patch using oxybutynin as a drug. The patch is enabled to achieve both skin absorption property of the drug and pharmaceutical physical properties at high levels by introducing, as adhesive base agents, an acrylic-based polymer and a rubber-based polymer at a specific mass ratio into an adhesive agent layer. Patent Literature 3 also states that the drug concentration in the adhesive agent layer may be a supersaturated concentration.